Delirium-Effectiveness and Safety of The Awakening and Breathing

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Crit Care Med. Author manuscript; available in PMC 2014 November 01.
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Crit Care Med. 2014 May ; 42(5): 1024–1036. doi:10.1097/CCM.0000000000000129.
Effectiveness and Safety of the Awakening and Breathing

Coordination, Delirium Monitoring/Management, and Early
Exercise/Mobility (ABCDE) Bundle
Michele C. Balas, PhD, RN, APRN-NP, CCRN1, Eduard E. Vasilevskis, MD, MPH2,3,4, Keith
M. Olsen, PharmD, FCCP, FCCM5,6, Kendra K. Schmid, PhD7, Valerie Shostrom, MS7,
Marlene Z. Cohen, PhD, RN, FAAN8, Gregory Peitz, PharmD, BCPS6,7, David E. Gannon,
MD, FACP, FCCP2, Joseph Sisson, MD9, James Sullivan, MD10, Joseph C. Stothert, MD,
PhD, FCCM, FACS11, Julie Lazure, BSN, RN12, Suzanne L. Nuss, PhD, RN13, Randeep S.
Jawa, MD, FACS, FCCM11, Frank Freihaut, RRT14, E. Wesley Ely, MD, MPH, FCCM3,4,15, and
William J. Burke, MD16
1The Ohio State University, College of Nursing, Center for Critical and Complex Care
2VanderbiltUniversity, Department of Medicine, Division of General Internal Medicine and Public
Health, Section of Hospital Medicine
3Vanderbilt University, Center for Health Services Research
4Tennessee Valley VA, Geriatric Research, Education, and Clinical Center (GRECC)
5University of Nebraska Medical Center, College of Pharmacy, Department of Pharmacy Practice
6The Nebraska Medical Center, Department of Pharmaceutical, and Nutrition Care
7University of Nebraska Medical Center, College of Public Health, Department of Biostatistics
8University of Nebraska Medical Center, College of Nursing, Department of Adult Health and
Illness
9University of Nebraska Medical Center, Department of Internal Medicine, Division of Pulmonary,
Critical Care, Sleep & Allergy
10University of Nebraska Medical Center, Department of Anesthesiology

11University of Nebraska Medical Center, Department of Surgery
12The Nebraska Medical Center, Department of Adult Critical Care Services
13The Nebraska Medical Center, Department of Nursing Research and Quality Outcomes
14The Nebraska Medical Center, Department of Respiratory Care
15Vanderbilt University, Department of Medicine, Division of Allergy, Pulmonary, and Critical Care
Medicine
Corresponding Author: Michele C. Balas, 350 Newton Hall, 1585 Neil Avenue Columbus, OH 43210; phone 614-688-2050; balas.
17@osu.edu.
The work was performed at The Nebraska Medical Center.
The remaining authors have disclosed that they do not have any potential conflicts of interest.
Balas et al. Page 2
16University of Nebraska Medical Center, Department of Psychiatry
Abstract
Objective—The debilitating and persistent effects of intensive care unit (ICU)-acquired delirium
and weakness warrant testing of prevention strategies. The purpose of this study was to evaluate
the effectiveness and safety of implementing the Awakening and Breathing Coordination,
Delirium monitoring/management, and Early exercise/mobility (ABCDE) bundle into everyday
practice.
Design—Eighteen-month, prospective, cohort, before-after study conducted between November

2010 and May 2012.
Setting—Five adult ICUs, one step-down unit, and one oncology/hematology special care unit
located in a 624-bed tertiary medical center.
Patients—Two hundred ninety-six patients (146 pre- and 150 post-bundle implementation), age
≥ 19 years, managed by the institutions’ medical or surgical critical care service.
Interventions—ABCDE bundle.
Measurements—For mechanically ventilated patients (n = 187), we examined the association

between bundle implementation and ventilator-free days. For all patients, we used regression
models to quantify the relationship between ABCDE bundle implementation and the prevalence/
duration of delirium and coma, early mobilization, mortality, time to discharge, and change in
residence. Safety outcomes and bundle adherence were monitored.
Main Results—Patients in the post-implementation period spent three more days breathing
without mechanical assistance than did those in the pre-implementation period (median [IQR], 24
[7 to 26] vs. 21 [0 to 25]; p = 0.04). After adjusting for age, sex, severity of illness, comorbidity,
and mechanical ventilation status, patients managed with the ABCDE bundle experienced a near
halving of the odds of delirium (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.33–0.93; p
= 0.03) and increased odds of mobilizing out of bed at least once during an ICU stay (OR, 2.11;
95% CI, 1.29–3.45; p = 0.003). No significant differences were noted in self-extubation or
reintubation rates.
Conclusions—Critically ill patients managed with the ABCDE bundle spent three more days
breathing without assistance, experienced less delirium, and were more likely to be mobilized
during their ICU stay than patients treated with usual care.
Keywords
ABCDE bundle; ventilator-free days; delirium; intensive care unit
INTRODUCTION
Growing evidence suggests that there is an iatrogenic component to intensive care unit
practice (ICU) that influences critically ill patients’ likelihood of experiencing ICU-acquired
delirium and weakness. These comorbidities are common in adult critically ill patients (1–7)
and independently predict increased mortality (1, 8–11), mechanical ventilator days (5, 10–
Balas et al. Page 3
12), ICU length of stay (12–14), and use of continuous sedation and physical restraints (15–
16). The effects of both conditions are often persistent and include functional decline (17)
and long-term cognitive impairment (18). Strategies are needed to prevent and/or treat ICU-
acquired delirium and weakness.
Mechanical ventilation, sedative medications, and immobilization are known risk factors for
ICU-acquired delirium and weakness (6–7, 19). When these factors interact with other
known predisposing factors, the likelihood of developing delirium and weakness rises (6–7,
20). Multicomponent approaches targeted to modifiable risk factors have effectively
prevented delirium among older hospitalized medical patients (21). Such multifaceted
interventions, however, are understudied in the ICU setting.
A multicomponent liberation and animation strategy aimed at reducing delirium and

weakness has recently been proposed (22–25). Liberation refers to reducing exposure to
mechanical ventilation and sedative medications through use of coordinated, target-based
sedation protocols, spontaneous awakening trials (SATs) (26), and spontaneous breathing
trials (SBTs) (27). Animation refers to early mobilization, which reduces delirium (28–30).
This evidence-based strategy is referred to as the ABCDE bundle: Awakening and Breathing
Coordination, Delirium monitoring/management, and Early exercise/mobility (22–25).
A bundle is a small set of evidence-based practices that, when performed collectively and
reliably, have been proven to improve patient outcomes (31). Bundles are used in the ICU
setting to address a number of serious iatrogenic conditions (e.g., ventilator-associated
pneumonia, central line infections). The use of bundles, as suggested in the 2013 Clinical
Practice Guidelines for the Management of Pain, Agitation, and Delirium (PAD) in Adult
Patients in the Intensive Care Unit (32), may be similarly beneficial for developing patient-
centered protocols for preventing and treating PAD in critically ill patients.
While many ABCDE bundle components improved important clinical outcomes in

rigorously-designed randomized controlled trials (RCTs), most of these RCTs evaluated the
safety and efficacy of these interventions in isolation, excluded many important ICU
populations, and generally relied on research staff to implement the intervention.
Additionally, the evidence supporting both the ABCDE bundle and the new PAD guideline
recommendations was based predominately on data derived from RCTs in mechanically
ventilated patients. Given these circumstances, there is great interest on the part of ICU
clinicians to know if the ABCDE approach will improve patient outcomes and which
patients the bundle should be applied to (e.g., intubated vs. non-intubated patients). These
are relevant questions considering that the vast majority of ICU patients are not
mechanically ventilated (33).
This study was designed to better understand these important aspects of the ABCDE
management strategy. Our goal was to determine if implementing the ABCDE components
as a bundle would prove safe and effective if applied to every critically ill patient, every day,
regardless of mechanical ventilation status, as well as to identify successes and pitfalls in
bundle implementation. Some results of the current study have been previously reported in
abstract form (34–36).
Balas et al. Page 4
METHODS
Additional information about the methods is provided in the online supplement.
Overview of Study Development and Adoption of ABCDE Bundle Policy

We recently described in detail our experience implementing the ABCDE management
strategy into everyday practice (37). In brief, over an 18-month period, members of the
research team and study site collaborated on the development of an institutional ABCDE
bundle policy and numerous ABCDE bundle-related educational opportunities (Table E1
online supplement). The ABCDE bundle was officially implemented on October 3, 2011.
Usual Care (Pre-ABCDE Bundle Implementation)

Prior to ABCDE bundle implementation, clinicians at the participating institution had some
experience with SATs and SBTs. The performance of both procedures, however, was
inconsistent and identified as a needed area of quality improvement. There were no official
policies in place to guide the SAT or SBT process (e.g., no checks to see if it was safe to
perform a SAT or SBT, no guidance as to what defined success or failure). Additionally,
SATs and SBTs were rarely coordinated, and interprofessional rounding depended on the
individual ICU physicians’ practice. No delirium monitoring or management policies were

in place. One ICU was in the beginning phase of an early mobility program, but patients
were not routinely assisted out of bed in the ICU setting.
ABCDE Bundle Intervention (Post-ABCDE Bundle Implementation)

In the post-implementation period, the stated institutional policy was that the ABCDE
bundle was to be applied to every adult patient receiving ICU level of care. All patients were
to receive the intervention on a daily basis unless a licensed prescriber wrote an order not to
have the patient participate in certain components of the ABCDE bundle (opt-out method).
The five distinct components of the ABCDE bundle, along with safety screen and success
failure criteria used in this study, are provided in Figure 1 and Table 1.
Study Design, Setting, and Participants

This prospective, before-after study was conducted at a 624-bed tertiary medical center.
Eligible patients included adult patients (≥19 years old) admitted to the institution’s medical
or surgical critical care service, regardless of mechanical ventilation status. Critically ill
patients were recruited consecutively from five adult ICUs, one step down unit, and an
oncology/hematology special care unit. Patients were excluded if they did not have a legally
authorized representative (LAR) to provide consent within 48 hours of ICU admission.
“Pre” patients were enrolled from February to October 2011 and received “usual care.”
“Post” patients were enrolled from October 2011 to April 2012. The institutional review
board approved the study protocol, and written informed consent was obtained from all
patients’ LAR.
Balas et al. Page 5
Study Procedures
To ensure reliability of outcomes assessment in the pre- and post- implementation period,
trained research personnel (all RNs) were hired to enroll patients, perform daily sedation/
agitation and delirium assessments, and conduct standardized medical record reviews. Inter-
rater reliability checks for delirium and sedation/agitation screenings were 100% for all four
research personnel. The research personnel had no role in administering any parts of the
ABCDE bundle. The decision to perform daily SATs, SBTs, delirium monitoring/
management, and early exercise/mobility was made solely by the ICU team.
At enrollment, we collected demographic data, admission source, and primary diagnosis.

Severity of illness and comorbidity were measured by the Acute Physiology and Chronic
Health Evaluation II (APACHE II) (38) score and Charlson Comorbidity Index (39),
respectively. We recorded the cumulative amount of sedative medications administered from
ICU admission until study enrollment, including operating room, post-anesthesia care unit,
and procedural sedation.
Awakening and Breathing Coordination—We recorded daily the total 24-hour dose
of sedative medications as we did at study enrollment. If a patient received a continuous
infusion of sedative medications and/or mechanical ventilation within the preceding 24-hour
period, we recorded whether that patient received a SAT/SBT and the documented reasons
for safety screen or trial failure. We recorded the date and time of intubation and extubation,
any unplanned extubations, reintubations, new tracheostomies, and any hospital discharges
on mechanical ventilation.
Delirium Monitoring/Management—The patients’ level of arousal was assessed daily

by research personnel with the Richmond Agitation-Sedation Scale (RASS) (40–41).
Subjects with a RASS score of −3 or higher underwent delirium screening with the
Confusion Assessment Method for the ICU (CAM-ICU) (2, 42). If the subject was
unavailable, additional attempts were made to evaluate their neurologic status that day. We
also recorded the results of the ICU clinicians’ every-8-hour CAM-ICU and RASS
assessments.
Early Exercise/Mobility—We recorded daily whether patients received physical therapy

consultation and if they were mobilized out of bed anytime in the previous 24 hours.
Outcome Definitions
Our primary outcome for mechanically ventilated patients was ventilator-free days (VFDs).
We defined VFDs as the number of days patients were breathing without mechanical
ventilator assistance during a 28-day period which began at the time of study enrollment. A
period of unassisted breathing began with extubation (or removal of mechanical ventilation
support for patients with tracheostomies) if the period of unassisted breathing lasted at least
48 consecutive hours. Patients who died during the study period were assigned 0 VFDs.
We secondarily examined outcomes across the entire ICU population (i.e., mechanically
ventilated and non-mechanically ventilated patients), including the prevalence, duration, and
Balas et al. Page 6
percent of ICU days of delirium and coma. Duration of delirium was defined as the number
of ICU days in which patients were CAM-ICU-positive and not comatose. Duration of coma
was defined as the number of ICU days that patients had a RASS score of −4 or −5. We
additionally explored the number of patients mobilized out of bed during their ICU stay.
Finally, we examined 28-day ICU and total hospital mortality, time to discharge from the
ICU and hospital, and the number of patients who experienced a change in residence.
Change in residence was defined as discharge from the hospital to a place other than home
in subjects residing at home prior to admission. Unplanned extubations, reintubations,
tracheostomy placement, percent of ICU time in physical restraints, and the use of imaging
for “changes in mental status” were tracked as safety endpoints. Reintubation was defined as
a second intubation that occurred during the patient’s initial ICU stay.
Statistical Analysis
Demographic and clinical characteristics were compared between both sets of subjects and
by mechanical ventilation status. Mean and standard deviation (median and interquartile
range [IQR] for skewed distributions) or frequencies and percentages are presented for
continuous or categorical variables, respectively. Initial comparisons between pre- and post-
groups were made using t tests (or Wilcoxon test) for continuous variables, chi-square (or
Fisher’s exact test) for categorical variables and log-rank tests for time-to-event variables.
Differences in outcomes between pre and post groups were analyzed after adjusting for age,
sex, mechanical ventilation status, APACHE II, and Charlson Comorbidity Index using
logistic regression for binary outcomes and Cox regression for time-to-event outcomes. SAS
version 9.2 was used for all summaries and analyses. The statistical level of significance was
set at < 0.05 (2-sided alpha).
RESULTS
Patient Characteristics
A total of 146 patients were enrolled before ABCDE bundle implementation (“pre” group)
and 150 after implementation (“post” group) (Figure 2). Patients in the pre-implementation
phase were older (pre-age mean 59.2 +/−16.1 vs. post-age mean 55.6 +/−14.9; p = 0.05), but
otherwise shared similar baseline characteristics to patients in the post-implementation
period (Table 2). Patients in both groups were lightly sedated at the time of study enrollment
(median RASS score of −1) and received similar doses and types of sedative medications
prior to study enrollment. Patients were admitted to the ICUs with a variety of medical and
surgical diagnoses, with more than 40% of the sample having surgery on or during their ICU
admission. When we examined baseline characteristics by mechanical ventilation status, no
significant differences pre- and post-implementation were noted (Table E2 online
supplement).
Outcomes-Effectiveness
Mechanically ventilated patients post-implementation spent more days breathing without
mechanical ventilator assistance than those pre-implementation (pre-median 21 days [IQR 0
to 25] vs. post-median 24 days [IQR 7 to 26]; p = 0.04) (Table 3). Three patients in the post-
Balas et al. Page 7
implementation and five in the pre-implementation period were discharged from the hospital
on mechanical ventilation (p = 0.50).
Fewer patients treated with the ABCDE bundle experienced delirium (pre 62.3% vs. post
48.7%; p = 0.02) (Table 3). Delirium duration was reduced by one day in the post-
implementation period, and the percent of ICU days spent delirious decreased by 17% (pre
50% [IQR 30 to 64.3] vs. post 33.3% [IQR 18.8 to 50]; p = 0.003). After adjusting for age,
APACHE II score, sex, Charlson Comorbidity Index, and mechanical ventilation, there
continued to be a significant effect of the ABCDE bundle on prevalence of delirium (p =
0.03), and the odds of delirium were reduced by almost half (OR: 0.55; 95% CI, 0.33–0.93).
No significant difference was noted in coma prevalence, coma duration, percentage of ICU
days spent in coma, or mean RASS score between the pre- and post-implementation period
in unadjusted or adjusted analyses.
Following multivariable adjustment, a significant effect of the ABCDE bundle was observed
on the percentage of patients (pre 48% vs. post 66%; p = 0.002) who were mobilized during
their ICU stay. Patients treated with the ABCDE bundle had twice the odds (95% CI, 1.30–
3.45; p = 0.003) of mobilizing out of bed at least once during their ICU stay compared to
patients in the ICU prior to bundle implementation (Table 3).
Unadjusted hospital mortality was significantly lower in the post-implementation group (p =

0.04), while ICU mortality showed a non-statistically significant reduction (p = 0.07). The
hospital mortality rate was 19.9% in the pre-implementation period vs. 11.3% in the post-
implementation period, yielding an odds ratio of 0.56 (95% CI 0.28–1.10; p = 0.09) after
adjustment for age, APACHE II score, sex, and comorbidity (Table 3).
No significant difference was observed in the time to ICU or hospital discharge between the
pre- and post-implementation periods (Table 3). Few ICU patients who were admitted from
home returned to this setting at hospital discharge in either the pre- or post-implementation
period. No significant differences, however, were noted in change in residence in either the
unadjusted or adjusted analysis.
Outcomes-Safety
No significant differences were found in unplanned extubations, reintubation rates,
tracheostomy placements, percent time spent in physical restraints, or the use of imaging for
mental status changes pre versus post ABCDE bundle implementation (Table 4).
ABCDE Bundle Compliance and Sedative Medication Use

Most patients requiring mechanical ventilation received a continuous infusion of either
sedative or opioid medications sometime during their ICU stay (pre 77.4% vs. post 70.2%, p
= 0.26) (Table 5). Post ABCDE bundle implementation, there was a significant increase in
the number of patients who had their continuously infused sedative medication held at least
once for a SAT (pre 53% vs. post 71%; p = 0.04). The percentage of ICU days on which
patients received a SAT while on a continuously infused opioid medication also doubled in
the post-implementation period (pre 25% vs. post 50%; p = 0.001). Patients in the post-
implementation period were significantly more likely to undergo a SBT at least once during
Balas et al. Page 8
their ICU stay (pre 71% vs. post 84%; p = 0.03). In the post-implementation period,
clinicians documented a variety of reasons for not performing both SATs and SBTs (Table
E3 online supplement).
While there was a trend toward decreased benzodiazepine use and increased opiate use in
the post-intervention period, the number of patients treated and total average daily doses of
these medications did not differ significantly pre- and post-implementation (Table 6). CAM-
ICU and RASS score were documented in the post-implementation period every 8 hours by
bedside nurses 50% and 68% of the time, respectively (Table 6). Delirium was identified as
present by bedside nurses in 51% of patients in the post-implementation period. While
nearly two-thirds of the patients received a physical therapy consultation while they were in
the ICU, approximately one-third of ICU days were spent out of bed.
DISCUSSION
We explored the effectiveness and safety of implementing into everyday clinical care an
interprofessional, multicomponent, bundle of evidence-based interventions directed at
reducing the harmful effects of over-sedation, mechanical ventilation, and immobility. In
this prospective before-after study, implementation of the ABCDE bundle resulted in
patients spending an additional three days breathing without mechanical ventilator

assistance compared to patients treated with usual care. After adjusting for important
covariates, the ABCDE bundle was found to be an important independent predictor of
reduced delirium rates and increased likelihood of mobilizing out of bed. Implementation of
the ABCDE bundle was also found to be safe and well tolerated. These efficacy and safety
findings were present despite a lower than anticipated compliance with the ABCDE bundle.
Our results are consistent with RCTs that studied the individual components of the ABCDE
bundle. Girard and colleagues (43) found that a ventilator liberation strategy pairing daily
SATs and SBTs resulted in three more VFDs and less time in coma compared to usual care
consisting of daily SBTs and patient-targeted sedation. We found a similar reduction in
VFDs but not in coma days. This may be due to deeper sedation levels at enrollment in the
Girard study (RASS of −4 compared to RASS of −1). Our findings are also consistent with
randomized trial evidence from Schweickert and colleagues (30) that found a rehabilitation
strategy consisting of SATs and physical and occupational therapy resulted in more VFDs
and shorter duration of delirium for mechanically ventilated patients who were functionally
independent prior to hospitalization.
In the current and previous investigations (30, 43), improvements in outcomes occurred
despite the fact that the overall number of patients treated with sedative and opioid
medications did not significantly differ between groups. This suggests (but does not prove)
the potential benefit from the “act” of awakening. This awakening strategy ensures a period
of maximum wakefulness that may mitigate harm through a variety of potential
mechanisms. For example, daily awakenings may reduce the risks of prolonged deep
sedation (44), provide beneficial effects of higher peak stimulations (45), and/or allow for
patients to engage in physical and cognitive activity (46) that may be independently
Balas et al. Page 9
protective. It is equally plausible that observed improvements were due to other factors such
as active care coordination or more intense delirium monitoring.
Despite intense education regarding the hazards of continuously infused sedation, more than
two-thirds of the patients in the current study were treated with this sedation strategy. While
clinicians in this study were more likely to discontinue sedative drips for a SAT after
ABCDE bundle implementation, there was no difference in SAT performance for patients
receiving opioid infusions, suggesting that clinicians may not view opioids as potentially
harmful, or alternatively, believe the need for pain medication outweighs the need to
discontinue sedation.
Similarly, despite the known benefits of early mobilization in mechanically ventilated

patients (28–30), patients spent more than 65% of their ICU days in bed. This finding may
be due to a number of factors, including the method by which early mobilization was
conducted (i.e., primarily by ICU RNs without additional staffing), the patients to which it
was applied (i.e., pre-hospitalization functional status not considered), and the outcomes that
were used to evaluate effectiveness. Patient outcomes, however, were significantly improved
despite lower-than-desired bundle adherence. Therefore, the current study may under-
represent the potential impact with ABCDE bundle implementation, considering that we did
not reach the goal of “applying it to every patient every day.” This also highlights the need
for rigorously designed research to understand best practices for applying evidence to the
bedside.
A major strength of this study was the daily assessment of patients’ sedation/agitation level
and delirium status by trained study staff using valid and reliable screening instruments.
Enhancing the applicability and feasibility for other ICUs, this study also included the
results of bedside RNs’ assessment of sedation levels and delirium status, demonstrating
good agreement between clinician and research personnel. In contrast to previous RCTs, our
study had few exclusion criteria. We included a diverse patient population (e.g., intubated
and non-intubated) and relied on clinicians to implement the interventions and monitor the
patients, suggesting that the ABCDE bundle could be applied widely across ICUs. We also
followed adherence to the individual components of the ABCDE bundle, critical to
understanding effectiveness trial results. Finally, study focus was on knowledge translation,
or applying research findings into everyday practice, an important yet understudied subject
area in critical care.
There are several important limitations to this investigation. Because of the study’s design,
relatively small sample size, and the fact that there was a delay in study enrollment until
consent was obtained, our results are susceptible to both temporal changes as well as the
impact of important unbalanced (or missing) confounders not included in our multivariable
adjustment. The fact that most ABCDE bundle-related educational efforts took place during
the pre-implementation period may have also influenced study findings. While we attempted
to track the number of patients who received individual components of the ABCDE bundle
each day, we were unable to determine the cause of coma (i.e., structural or drug-induced)
and relied on medical record reviews, which limited our ability to determine definitively the
reasons for withholding specific interventions. This was particularly true in the pre-
Balas et al. Page 10
implementation period, when there were no SAT or SBT safety screen criteria. Finally, we
also did not follow pain levels using a valid and reliable tool as suggested in the new PAD
guidelines. These limitations, in balance with the observed intervention benefit, suggest the
value of confirmative trials.
While we followed a number of important effectiveness and safety outcomes, some applied
to only to a segment of the ICU population (e.g., VFDs to mechanically ventilated patients),
while others could be interpreted as either an outcome or compliance measure (e.g.,
mobilized out of bed anytime). Future studies would be strengthened by the use of a
validated functional outcome measure. We also did not explore the role that specific
sedative medications had on patient outcomes, but this is an appropriate direction for future
analysis. Finally, it is important to reiterate that nearly all the evidence supporting the
ABCDE bundle (and new PAD guidelines) was derived from RCTs that included only
mechanically ventilated patients. Our inclusion of non-intubated patients extrapolated
evidence derived from one population (mechanically ventilated patients) to a population less
well studied (non-mechanically ventilated patients). While we found benefits and no
obvious harm applying the ABCDE bundle to non-intubated patients, we believe individual
ICUs should explore their own epidemiology/patient mix, culture, and staffing levels before
they decide whether to apply the ABCDE bundle to their entire ICU population. Our data
also suggest that RCTs may be warranted in non-mechanically ventilated patients to
strengthen the PAD evidence base.
CONCLUSIONS
This prospective study explored the effectiveness and safety of the ABCDE bundle, an
evidence-based, interprofessional, multicomponent ICU management strategy that promotes
early liberation and animation of critically ill patients. In a diverse group of critically ill
patients, implementation of the ABCDE bundle resulted in reduced time on the ventilator,
less delirium, and more time spent out of bed compared to patients not treated with the
bundle. These improvements were achieved despite little difference in medication exposure
and incomplete bundle adherence. The ABCDE bundle appears to be a valuable tool in the
management of critically ill patients.
Supplementary Material
Refer to Web version on PubMed Central for supplementary material.
Acknowledgments
The authors are grateful for all the support provided by nurses, respiratory therapists, pharmacists, physical
therapists, physicians, and administrative leadership at the Nebraska Medical Center. We are also deeply
appreciative of the patients, families, and research staff who made this study possible.
The study was supported by the Robert Wood Johnson Foundation (RWJF) Interdisciplinary Nursing Quality
Research Initiative (INRQI). Research reported in this publication was also supported by the National Institute on
Aging (NIA) of the National Institutes of Health (NIH) under Award Number K23AG040157. The content is solely
the responsibility of the authors and does not necessarily represent the official views of the National Institutes of
Health.
Conflicts of Interest and Source of Funding: Dr. Balas is currently a Co-investigator on a grant supported by the
Alzheimer’s Association and has received honoraria from ProCe, the France Foundation, Hospira, and Hillrom. Dr.
Vasilevskis is currently receiving a Career Development Award from the NIH-NIA (K23AG040157). Dr. Sisson is
currently receiving a NIH Grant (AA008769-20A1). Dr. Schmid serves as a consultant on the data safety and
monitoring board (DSMB) for Puma Biotechnology and, in the past, served as a DSMB consultant for Pfizer. Dr.
Ely received support from NIA AG-027472 and AG-035117, and he has received honoraria from Hospira, Abbott,
and Orion. Dr. Burke has received grant support for clinical studies from the National Institute of Mental Health,
National Institute on Aging, RWJF, Alzheimer Disease Cooperative Studies (ADCS), Forest Laboratories Inc.,
Astra Zeneca, Vanda Pharmaceuticals, Neosync Inc., Elan/Wyeth/Janssen, Baxter Health Care Corporation, Pfizer
Inc., Noven Pharmaceuticals, and Novartis. For the remaining authors, none were declared.
Copyright Form Disclosures:
Dr. Balas’ institution received grant support from the RWJF INQRI and the Alzheimer’s Association (Co-I on
mobile monitoring study). Dr. Balas received support for article research from the RWJF INQRI.
Dr. Vasilevskis received grant support from NIH-NIA 5K23AG040157 (Career Development Award) and support
for article research from NIH.
Dr. Olsen’s institution received grant support from the RWJF (supported in part, the research related to this
manuscript). Dr. Olsen received support for article research from the RWJF.
Dr. Schmid’s institution received grant support from the RWJF INQRI. Dr. Schmid consulted for Puma
Biotechnology and Pfizer (Data Safety Monitoring Committee member) and received support for article research
from the RWJF.
Marlene Z. Cohen C/F (institution received grant support from the RWJF; received support for article research from
the RWJF).
Dr. Sullivan received support for article research from the RWJF.
Dr. Jawa disclosed that this study was supported by a grant from the RWJF INQRI, but he did not receive any
compensation from this grant.
Dr. Ely consulted for Cumberland and Masimo, received grant support from Lilly, and lectured for Hospira.
Dr. Burke’s institution received support for travel (funds to attend INQRI annual meeting) from the RWJF and
grant support from the RWJF (for the research), NIMH (R01 funding), Alzheimer Disease Cooperative Study
(ADCS) in collaboration with NIMH and Baxter (grant funds), Pfizer (clinical trial funding), Neosync (clinical trial
funding), Vanda Pharmaceuticals (clinical trial funding), Novartis (clinical trial funding), Elan/Wyeth (clinical trial
funding), Noven Pharmaceuticals(clinical trial funding), Astra Zeneca (clinical trial funding), and Elan (clinical
trial funding).
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Figure 1. ABCDE Bundle Policy

RN = Registered Nurse, RT = Respiratory Therapist, PT = Physical Therapist, SAT =
Spontaneous Awakening Trial; SBT = Spontaneous Breathing Trial; RASS = Richmond
Agitation-Sedation Scale; CAM-ICU = Confusion Assessment Method for the Intensive
Care Unit.
aContinuous sedative medications maintained at previous rate if SAT safety screen failure.
Mechanical ventilation continued, and continuous sedative medications restarted at half the
previous dose only if needed due to SBT safety screen failure.
bContinuous sedative infusions stopped, and sedative boluses held. Bolus doses of opioid
medications allowed for pain. Continuous opioid infusions maintained only if needed for
active pain.
cContinuous sedative medications restarted at half the previous dose, and then titrated to
sedation target if SAT failed. Interdisciplinary team determines possible causes of SAT/SBT
failure during rounds. Mechanical ventilation restarted at previous settings, and continuous
sedative medications restarted at half the previous dose only if needed if SBT failed.
dSAT pass if the patient is able to open his/her eyes to verbal stimulation without failure
criteria (regardless of trial length) or does not display any of the failure criteria after four
hours of shutting off sedation.
eEach day on interdisciplinary rounds, the RN will inform the team of the patient’s target
RASS score, actual RASS score, CAM-ICU status, and sedative and analgesic medications
the patients is receiving. If delirium is detected, team will discuss possible causes, eliminate
risk factors, and employ non-pharmacologic management strategies.
fEach eligible patient is encouraged to be mobile at least once a day, with the specific level
of activity geared to his or her readiness. Patients progress through a three-step process,
embarking on the highest level of physical activity they can tolerate. Progress includes
sitting on edge of bed, standing at bedside and sitting in chair, and walking a short distance.
Use of the protocol ends when the patient is discharged from the ICU.
Figure 2. PATIENT FLOW DIAGRAM

LAR = Legally Authorized Representative.
Table 1
ABCDE Bundle Safety Screen Questions and Success/Fail Criteria

ABCDE Bundle Safety Screen Criteria- Pass/Fail Criteria-

Component Conditions for exclusion Conditions denoting failure
Spontaneous Awakening Trial 1 Active seizures 1 RASS score >2 for ≥5 minutes
2 Alcohol withdrawal 2 Pulse-ox. <88% for ≥5 minutes
3 Neuromuscular blockade 3 Respirations >35 breaths per minute for ≥5
minutes
4 Control of increased ICP
4 Acute cardiac arrhythmia
5 ICP >20 mm Hg
5 ICP >20 mm Hg
6 Receiving ECMO
6 Two or more of the following: (heart rate
7 Documentation of MI in past 24 hours increase ≥20 per minute BPM, heart rate <
55 BPM, use of accessory muscles,
8 Current RASS >2
abdominal paradox, diaphoresis or
dyspnea)
Spontaneous Breathing Trial 1 Chronic ventilator dependence 1 Respiratory rate >35 breaths per minute for
≥5 minutes
2 Pulse ox. reading <88%
2 Respiratory rate <8
3 FiO2 >50%
3 Pulse ox. <88% > 5 minutes
4 Set PEEP >7

4 ICP >20 mm Hg
5 ICP >20 mm Hg
5 Mental status changes
6 Receiving mechanical ventilation in
an attempt to control ICP 6 Acute cardiac arrhythmia
7 Documentation of MI in past 24 hours 7 2 or more of the following: (use of
accessory muscles, abdominal paradox,
8 Increasing doses of vasopressor diaphoresis, dyspnea.
medications
9 Lack of inspiratory effort
Early Exercise/Mobility 1 RASS <−3 1 Symptomatic drop in mean arterial pressure

2 FIO2>0.6 2 Heart rate <50 or >130 BPM ≥5 minutes
3 Set PEEP>10 cm H20 3 Respiratory rate <5 or >40 breaths per
minute ≥5 minutes
4 Increasing doses of vasopressor
infusions in the last 2 hours 4 Systolic blood pressure >180 mm Hg ≥5
minutes
5 Evidence of active MI
5 Pulse oximetry reading <88% ≥5 minutes
6 Administration of a new
antiarrhythmic agent 6 Marked ventilator dyssynchrony
7 Receiving therapies that restricted 7 Patient distress
mobility (e.g., ECMO, open-

abdomen, etc.) 8 New arrhythmia or evidence of active MI
8 Injuries in which mobility is 9 Concern for airway device integrity or

contraindicated (e.g., unstable endotracheal removal
fractures, etc.)
10 Fall to knees
ABCDE = Awakening and Breathing Coordination, Delirium Monitoring/Management, and Early Mobility Bundle; Richmond Agitation-Sedation
Scale; ICP = Intracranial Pressure; ECMO = Extracorporeal Membrane Oxygenation; MI = myocardial ischemia; BPM = Beats per Minute; FiO2 =
Fraction of inspired oxygen; PEEP = positive end expiratory pressure; Pulse-ox = Pulse oximetry reading.
Table 2
Baseline Patient Characteristics

Pre-ABCDE Post-ABCDE
Characteristic Bundle Bundle p-value
N = 146 N = 150
Agea, mean (SD) yr 59.2 (± 16.1) 55.6 (± 14.9) 0.05
Female, n (%) 67 (45.9) 64 (42.7) 0.58

Caucasian, n (%) 134 (93.1) 133 (89.3) 0.25
Residence preadmissionb, n (%) 0.09
Home 118 (80.8) 132 (88.0)

Nursing home 7 (4.8) 7 (4.7)
Skilled nursing facility 4 (2.7) 6 (4.0)
Rehabilitation center 5 (3.4) 0 (0)
Other hospital 9 (6.2) 1 (0.7)
Other 3 (2.1) 4 (2.7)
APACHE II score, median (IQR) 23.5 (17 to 29) 21 (16 to 28) 0.08
Charlson Comorbidity Index, median (IQR) 2 (1 to 5) 2 (1 to 4) 0.48
Admitting ICU diagnosis, n (%) NT
Medicalc
Shock 20 (13.7) 20 (13.3)
Respiratory 37 (25.3) 35 (23.3)
Cardiac 6 (4.1) 5 (3.3)
Neurologic/other 25 (17.1) 34 (22.7)
Surgicald
Neurosurgical 29 (19.9) 24 (16.0)
Cardiothoracic/vascular 6 (4.1) 20 (13.3)
General surgery/trauma 21 (14.4) 11 (7.3)
Other 2 (1.4) 1 (0.7)
Admission type (elective), n (%) 30 (20.6%) 39 (26.0%) 0.27
Sedation before enrollment median (IQR)
Benzodiazepinese (mg) 7.2 (2 to 24) 8.8 (2 to 26.8) 0.91
Opiate (mg)f 16.7 (6.7 to 42.7) 26.7 (10 to 47) 0.27

Propofol (mg) 230 (100 to 1260) 200 (100 to 480) 0.48

Dexmedetomidine (ug) 1034 (748 to 1320) 78 (35 to 184) 0.06
Haloperidol (mg) 5 (n = 1) 1 (n = 1) NT
Surgery on/during ICU admission 63 (44.4%) 70 (46.7%) 0.69
RASS on first study day −1 (−3 to 0) N = 121 −1 (−3 to 0) N = 131 0.99
APACHE = Acute Physiology and Chronic Health Evaluation; ICU = intensive care unit; IQR = interquartile range; N = number; NT = not tested
(not enough subjects); mg = milligram; RASS = Richmond Agitation-Sedation Scale; SD = standard deviation; yr = year; ug = microgram
a
When age was examined by mechanical ventilation status, no significant differences were noted (Mechanically ventilated patients age pre 57.7 +/
−16.2 vs. post 55.4 +/−14.5, p = 0.30; Non mechanically ventilated patients age pre 61.7 +/−15.8 vs. post 56 +/−15.7, p = 0.06).
b
Data were re-categorized as home/other for purposes of statistical analysis.
c
Medical category described fully in online supplement.
d
Surgical category described fully in online supplement.
e
Expressed in lorazepam equivalents. Includes the following medications: lorazepam, midazolam, clonazepam, diazepam, temazepam. The total
dose includes continuous infusions and bolus doses given intravenously, intramuscularly, and orally.
f
Expressed in morphine equivalents. Includes the following medications: morphine, hydromorphone, and fentanyl. The total dose includes
continuous infusions and bolus doses given intravenously, intramuscularly, and orally.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Table 3
Main Study Outcomes
ABCDE Bundle Component Pre ABCDE Post ABCDE Unadjusted Adjusted Odds Adjusted p-
Balas et al.
Outcome Bundle Bundle p value Ratio value

N = 146 N = 150
Awakening and Breathing Coordinationa
Ventilator-free daysa
Mean (SD) 15 (11.4) 18 (10.6)
Median (IQR) 21 (0 to 25) 24 (7 to 26) 0.04
Delirium Monitoring/Management
Delirium anytime, n (%) 91 (62.3%) 73 (48.7%) 0.02 0.55b (0.33–0.93) 0.03
Duration of delirium, days, median (IQR) 3 (1 to 6) 2 (1 to 4) 0.52

Percent ICU days spent delirious, median (IQR) 50 (30 to 64.3) 33.3 (18.8 to 50) 0.003
Coma anytime, n (%) 41 (28.1%) 43 (28.7%) 0.91 1.00b 0.99
Coma days, median (IQR) 2 (1 to 4) 2 (1 to 5) 0.35

Percent ICU days spent in coma, median (IQR) 25 (18.2 to 44.4) 25 (12.5 to 42.9) 0.89
Richmond Agitation-Sedation Scale Score, mean (SD) 0.02 (1.4) −1.03 (1.2) 0.38
Early Exercise/Mobility
Mobilized out of bed anytime in ICU, n (%) 70 (48%) 99 (66.0%) 0.002 2.11b (1.30–3.45) 0.003
28-day Mortalityc
Hospital mortality (ICU and post-ICU), n (%) 29 (19.9%) 17 (11.3%) 0.04 0.56b (0.28–1.10) 0.09
ICU mortality, n (%) 24 (16.4%) 14 (9.3%) 0.07
Time to discharged (days)
From ICU, median (IQR) 5 (3, 8) 4 (3, 5) 0.21 1.16e (0.89–1.50) 0.27
From hospital, median (IQR) 13 (9, 15) 11 (9, 13) 0.99 1.01e (0.77–1.31) 0.96
Residence at hospital dischargef, n (%) 0.86
Home 51 (44%) 60 (45.1%)

Nursing home 9 (7.8%) 8 (6%)
Skilled nursing facility 13 (11.2%) 16 (12%)
Rehabilitation center 29 (25%) 27 (20.3%)
Page 21
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
ABCDE Bundle Component Pre ABCDE Post ABCDE Unadjusted Adjusted Odds Adjusted p-
Outcome Bundle Bundle p value Ratio value
N = 146 N = 150
Home with hospice 1 (0.9%) 2 (1.5%)
Hospice center 2 (1.7%) 4 (3%)
Balas et al.
Swing bed/other hospital 8 (6.9%) 6 (4.5%)

Other 3 (2.6%) 10 (7.5%)
Change in residence for those who came from homeg, n (%) 72 (61%) 72 (54.6%) 0.30 1.16b (0.66–2.03) 0.60
ICU = intensive care unit; IQR = interquartile range; n = number; SD = standard deviation.
a
For those subjects that received mechanical ventilation only pre N = 93 post N = 94.
b
Odds ratio and 95% Wald confidence limits.
c
All subjects who died did so within 28 days post-enrollment.
d
Time to ICU discharge is calculated only for the 28-day interval post enrollment. If a subject was not discharged within the first 28 days or died within 28 days, then she/he was considered censored.
e
Hazard ratio and 95% Hazard ratio confidence limits.
f
Data were categorized as home/other for purposes of statistical analysis.
g
Change in residence was defined as discharge from the hospital to a place other than home in those subjects residing at home prior to hospital admission.
Page 22
Table 4
Safety Outcomes
Pre ABCDE Post ABCDE

Safety Outcome Bundle Bundle p-Value
N = 93 N = 94
Any unplanned extubation 7 (7.5%) 7 (7.5%) 0.98
Any self-extubationa 6 (6.5%) 5 (5.3%) 0.74
Self-extubation requiring re-intubationa 1 (1.1%) 1 (1.1%) 0.99
Any re-intubation 16 (17.2%) 11 (11.7%) 0.28

Tracheostomy 15 (16.1%) 14 (14.9%)
Underwent imaging related to change in mental statusb 21 (14.4%) 17 (11.3%) 0.43
Percent of ICU time in physical restraints (median, interquartile range)b 12.7% (0–51.4%) 6.9% (0–50%) 0.29
Note:
a
Defined as an extubation documented to be done by patient.
b
For all patients included in study: pre n = 146 post n = 150.
Table 5
Spontaneous Awakening and Breathing Trial Implementation

Mechanically Ventilated Patients
Pre-ABCDE Post-ABCDE
Variable Bundle Bundle p-value
N = 93 N = 94
Received a continuously infused sedative medicationa anytime during ICU stay, n (%) 67 (72%) 59 (62.8%) 0.18
Had continuously infused sedative medicationa held at least once for a spontaneous awakening 35 (53%) 42 (71.2%) 0.04
trial (SAT), n (%)
SATs performed on eligible days (sedative medicationa only), median % (IQR) 42.9 (25, 66.7) 50 (33.3, 55.6) 0.38
Received a continuously infused opioid medicationb anytime during ICU stay, n (%) 34 (36.6%) 30 (31.9%) 0.50
Had continuously infused opioid medicationb held at least once for a SAT, n (%) 15 (45.5%) 18 (60%) 0.25
SATs performed on eligible days (opioid medicationb only), median % (IQR) 25 (14.3, 40) 50 (45.2, 66.7) 0.001
Received a continuously infused sedativea or opioidb medication anytime during ICU stay, n 72 (77.4%) 66 (70.2%) 0.26
(%)
Had continuously infused sedativea or opioidb medication held at least once for a SAT, n (%) 36 (50.7%) 42 (63.6%) 0.13
SATs performed on eligible days (sedativea or opioidb medication held), median % (IQR) 33.3 (24.4, 52.8) 50 (33.3, 50) 0.18
Underwent a spontaneous breathing trial (SBT) anytime during ICU stay, n (%) 65 (70.7%) 79 (84%) 0.03
SBT/mechanical ventilation days, median (IQR) 50 (31.8, 66.7) 50 (33.3, 66.7) 0.94
ICU = intensive care unit; IQR = interquartile range; n = number; SAT = spontaneous awakening trial; SBT = spontaneous breathing trial.
a
Includes the following medications: lorazepam, midazolam, propofol, and dexmedetomidine.
b
Includes the following medications: morphine, hydromorphone, and fentanyl.
Table 6
Sedative Medication Utilization and Delirium Monitoring/Management and Early Exercise/Mobility

Implementation
Variable Pre ABCDE Bundle Post ABCDE Bundle p-value

N = 146 N = 150
Sedation received post-enrollment
Benzodiazepinesa
Patients treated, n (%) 91 (62.3%) 77 (51.3%) 0.06
Total dose (mg), median (IQR) 21.2 (3, 87.6) 17.4 (3, 56.1) 0.41
Average daily doseb (mg), median (IQR) 2.8 (1, 12.7) 1.7 (0.4, 7.8) 0.09
Opiatesc
Total dose (mg), median (IQR) 26.3 (10, 147.2) 35.8 (14, 126) 0.70
Average daily doseb (mg), median (IQR) 5.8 (2, 16.7) 5.5 (2.2, 14.3) 0.97
Propofol
Total dose (mg), median (IQR) 1003 (150, 5305) 410 (140, 2310) 0.50
Average daily doseb (mg), median (IQR) 83.3 (10, 499.8) 66.7 (7.7, 419) 0.64
Dexmedetomidine (ug)
Total dose (mg), median (IQR) 1538 (566, 5820.3) 2500 (332, 3726) 0.69
Average daily doseb (mg), median (IQR) 140.3 (88.4, 269.3) 185.7 (28.4, 294.9) 0.87
Haloperidol
Total dose (mg), median (IQR) 6 (2.5, 19.5) 17.5 (3.8, 39.3) 0.24
Average daily doseb (mg), median (IQR) 0.5 (0.3, 1.3) 1.3 (0.4, 4.1) 0.20
Percentage of time CAM-ICU results documented every 8 hours by bedside ----- 50 (33.3, 66.7)
nursed
Mechanically ventilated (MV) patients, median (IQR) ---- 50 (33.3, 66.7)
Non-MV patients, median (IQR) ----- 60 (33.3, 68.6)
Delirium anytime per bedside nurse documentation, n (%) 76 (51%)
Percentage of time RASS score documented every 8 hours by bedside nurse 66.3% 68% 0.84 0.68
Richmond Agitation-Sedation Scale Score by bedside nurses, mean (SD) −0.64 (1.1) −0.59 (1.1)
Physical therapy consults anytime during ICU stay, n (%) 105 (71.9%) 113 (75.3%) 0.50
Mobilized out of bed (OOB) at least once during ICU stay, n (%) 70 (48%) 99 (66.0%) 0.002
Mechanically ventilated patients, n (%) 44/93 (47.3%) 57/94 (60.6%) 0.07
Non mechanically-ventilated patients, N (%) 26/53 (49.1%) 42/56 (75%) 0.005
OOB days/ICU length of stay, median % (IQR) 33.3 (16.7, 50) 33.3 (20, 53.9) 0.64
CAM = confusion assessment method; ICU = intensive care unit; IQR = interquartile range; mg = milligram; MV = mechanically ventilated; n =
number; OOB = out of bed; ug = microgram.
a
Expressed in lorazepam equivalents. Includes the following medications: lorazepam, midazolam, clonazepam, diazepam, temazepam. The total
dose includes continuous infusions and bolus doses given intravenously, intramuscularly, and orally.
b
Average daily dose calculated by taking the total dose per subject and dividing by their total days in ICU.
c
Expressed in morphine equivalents. Includes the following medications: morphine, hydromorphone, and fentanyl. The total dose includes
continuous infusions and bolus doses given intravenously, intramuscularly, and orally.
d
Per the institution’s ABCDE bundle policy, bedside nurses were required to document results of the CAM-ICU every 8 hours.

Delirium-Effectiveness and Safety of The Awakening and Breathing

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Delirium-Effectiveness and Safety of The Awakening and Breathing

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Crit Care Med. 2014 May ; 42(5): 1024–1036. doi:10.1097/CCM.0000000000000129.

Effectiveness and Safety of the Awakening and Breathing

10University of Nebraska Medical Center, Department of Anesthesiology

16University of Nebraska Medical Center, Department of Psychiatry

Design—Eighteen-month, prospective, cohort, before-after study conducted between November

Measurements—For mechanically ventilated patients (n = 187), we examined the association

acquired delirium and weakness.

A multicomponent liberation and animation strategy aimed at reducing delirium and

Coordination, Delirium monitoring/management, and Early exercise/mobility (22–25).

While many ABCDE bundle components improved important clinical outcomes in

Overview of Study Development and Adoption of ABCDE Bundle Policy

Usual Care (Pre-ABCDE Bundle Implementation)

individual ICU physicians’ practice. No delirium monitoring or management policies were

ABCDE Bundle Intervention (Post-ABCDE Bundle Implementation)

Study Design, Setting, and Participants

At enrollment, we collected demographic data, admission source, and primary diagnosis.

Delirium Monitoring/Management—The patients’ level of arousal was assessed daily

Early Exercise/Mobility—We recorded daily whether patients received physical therapy

patients in the ICU prior to bundle implementation (Table 3).

Unadjusted hospital mortality was significantly lower in the post-implementation group (p =

ABCDE Bundle Compliance and Sedative Medication Use

patients spending an additional three days breathing without mechanical ventilator

Similarly, despite the known benefits of early mobilization in mechanically ventilated

area in critical care.

value of confirmative trials.

Refer to Web version on PubMed Central for supplementary material.

Copyright Form Disclosures:

1344. [PubMed: 12421743]

Figure 1. ABCDE Bundle Policy

Figure 2. PATIENT FLOW DIAGRAM

ABCDE Bundle Safety Screen Questions and Success/Fail Criteria

ABCDE Bundle Safety Screen Criteria- Pass/Fail Criteria-

4 Set PEEP >7

Early Exercise/Mobility 1 RASS <−3 1 Symptomatic drop in mean arterial pressure

mobility (e.g., ECMO, open-

8 Injuries in which mobility is 9 Concern for airway device integrity or

Baseline Patient Characteristics

Agea, mean (SD) yr 59.2 (± 16.1) 55.6 (± 14.9) 0.05

Female, n (%) 67 (45.9) 64 (42.7) 0.58

Residence preadmissionb, n (%) 0.09

Home 118 (80.8) 132 (88.0)

Admitting ICU diagnosis, n (%) NT

Benzodiazepinese (mg) 7.2 (2 to 24) 8.8 (2 to 26.8) 0.91

Opiate (mg)f 16.7 (6.7 to 42.7) 26.7 (10 to 47) 0.27

Propofol (mg) 230 (100 to 1260) 200 (100 to 480) 0.48

Main Study Outcomes

Outcome Bundle Bundle p value Ratio value

Awakening and Breathing Coordinationa

Duration of delirium, days, median (IQR) 3 (1 to 6) 2 (1 to 4) 0.52

Coma days, median (IQR) 2 (1 to 4) 2 (1 to 5) 0.35

ICU mortality, n (%) 24 (16.4%) 14 (9.3%) 0.07

Time to discharged (days)

Residence at hospital dischargef, n (%) 0.86

Home 51 (44%) 60 (45.1%)

Swing bed/other hospital 8 (6.9%) 6 (4.5%)

Pre ABCDE Post ABCDE

Any self-extubationa 6 (6.5%) 5 (5.3%) 0.74

Self-extubation requiring re-intubationa 1 (1.1%) 1 (1.1%) 0.99

Any re-intubation 16 (17.2%) 11 (11.7%) 0.28

Underwent imaging related to change in mental statusb 21 (14.4%) 17 (11.3%) 0.43

Spontaneous Awakening and Breathing Trial Implementation

Mechanically Ventilated Patients